Radiation therapy to metastatic or primary liver tumors is limited by hepatic tolerance of radiation. In previous experiments we have established a model for radiation hepatitis in the rat. Utilizing a 1500 rad single dose directly to the liver we demonstrated abnormalities in all parameters measured: albumin space index, colloidal gold clearance, alkaline phosphatase, and histology. Animals receiving Depo- heparin in dose ranges reasonable for human application had essentially normal isotopic and chemistry values and more normal histology then those animals not receiving the heparin. We propose to expand our work to test its clinical applicability and to obtain further information on the pathogenesis of radiation hepatitis. We will modify our irradiation schedule to simulate more closely the clinical situation by using fractionated radiation therapy (daily treatments). Using the fractionated therapy model, we will refine our previous experiments with Depo-heparin to further quantitate and characterize the radioprotective effect. Having established the radioprotective effect of full therapeutic doses of heparin, we will test whether the heparin dose can be reduced without loss of protection. There is considerable evidence that so-called "mini-dose" heparin therapy has a significant protective effect against the formation of venous thrombi and subsequent pulmonary embolization in man. This "mini-dose" effect could also hold true for radiation hepatitis, and would be much safer to give to cancer patients as it would be accompanied by fewer hemorrhagic side effects. Using I- 125 fibrinogen we will study the time and dose relationships of fibrin clot formation in irradiated liver and attempt to relate this to the pathological lesions of radiation hepatitis. We shall then determine the effect of heparin on this process. At the time of this writing (December 1974) we have already obtained new information on the nature of radiation injury to the liver and its time course.